Walking-related ischemia-reperfusion in people with peripheral artery disease (PAD) is associated with calf skeletal muscle fiber atrophy and impaired mitochondrial function. These calf muscle abnormalities are associated with functional impairment and mobility loss in people with PAD. Yet few medical therapies exist to improve mobility or prevent disability in PAD patients. Recent evidence suggests that the angiotensin receptor blocker (ARB) telmisartan may reverse the skeletal muscle abnormalities present in PAD. In normal mice, telmisartan increases the quantity of Type I skeletal muscle fibers, improves mitochondrial function, increases oxygen consumption, and enhances exercise performance. Also in mice, ARBs reduce fibrosis after muscle injury and enhance satellite cell-dependent muscle regeneration after muscle injury. We hypothesize that these favorable effects on skeletal muscle in mice may repair the ischemia-reperfusion related calf muscle injury observed in patients with PAD. In support of our hypothesis, a small pilot trial in humans showed that telmisartan improved treadmill walking performance in people with PAD. The primary aims of the TELEX Trial are to definitively establish a) whether telmisartan alone improves walking performance in people with PAD compared to placebo and b) whether the combination of telmisartan plus supervised exercise improves walking performance more than telmisartan alone and supervised exercise alone, respectively. To achieve our aims, we will conduct a randomized controlled clinical trial (2 x 2 factorial design) of 240 PAD participants randomized to one of four arms: Group A: telmisartan + supervised exercise therapy; Group B: telmisartan + a no exercise control group; Group C: placebo + supervised exercise therapy; and Group D: placebo + a no exercise control group. Our primary outcome is change in six-minute walk performance between baseline and 6-month follow-up. Our secondary aims will measure change in treadmill walking performance, patient-reported walking performance (measured by the Walking Impairment Questionnaire), and quality of life (measured by the Short Form-36 Physical Functioning score). In exploratory aims, we will obtain calf muscle biopsies to delineate biologic pathways by which these therapies improve functioning. In addition to establishing the therapeutic benefit of telmisartan with and without exercise, the TELEX Trial will identify biological pathways associated with improved functional performance in people with PAD.